Journal Article

DZNE-2023-00136

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model.

Njavro, J. (First author)DZNE* ; Vukicevic, M. ; Fiorini, E. ; Dinkel, L.DZNE* ; Müller, S. A.DZNE* ; Berghofer, A.Extern* ; Bordier, C.DZNE* ; Kozlov, S.DZNE* ; Halle, A.DZNE* ; Buschmann, K.Extern* ; Capell, A.Extern* ; Giudici, C.DZNE* ; Willem, M.Extern* ; Feederle, R.DZNE* ; Lichtenthaler, S. F.DZNE* ; Babolin, C. ; Montanari, P. ; Pfeifer, A. ; Kosco-Vilbois, M. ; Tahirovic, S. (Last author)DZNE*

2022
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/cells12010079

Abstract: Amyloid-β (Aβ) deposition is an initiating factor in Alzheimer's disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ plaques, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating the phagocytic function of immune cells. Immunotherapies are currently pursued as strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. Here, we evaluated the effect of the Aβ targeting ACI-24 vaccine in reducing AD pathology in an amyloidosis mouse model. ACI-24 vaccination elicited a robust and sustained antibody response in APPPS1 mice with an accompanying reduction of Aβ plaque load, Aβ plaque-associated ApoE and dystrophic neurites as compared to non-vaccinated controls. Furthermore, an increased number of NLRP3-positive plaque-associated microglia was observed following ACI-24 vaccination. In contrast to this local microglial activation at Aβ plaques, we observed a more ramified morphology of Aβ plaque-distant microglia compared to non-vaccinated controls. Accordingly, bulk transcriptomic analysis revealed a trend towards the reduced expression of several disease-associated microglia (DAM) signatures that is in line with the reduced Aβ plaque load triggered by ACI-24 vaccination. Our study demonstrates that administration of the Aβ targeting vaccine ACI-24 reduces AD pathology, suggesting its use as a safe and cost-effective AD therapeutic intervention.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Microglia: metabolism (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Mice, Transgenic (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: therapy (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Amyloidosis: metabolism (MeSH) ; Plaque, Amyloid: metabolism (MeSH) ; Phenotype (MeSH) ; Vaccination (MeSH) ; Alzheimer’s disease ; ACI-24 ; Alzheimer’s disease ; Aβ vaccine ; immunotherapy ; microglia ; Amyloid beta-Protein Precursor ; Amyloid beta-Peptides ; Aβ vaccine

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Contributing Institute(s):

1. Ex vivo models (AG Tahirovic)
2. Neuroproteomics (AG Lichtenthaler)
3. Microglia and Neuroinflammation (AG Halle)
4. ALS, FTLD and Zebrafish models (AG Haass old)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022

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Database coverage:
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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Müller, S. A. (Corresponding author)DZNE* ; Lichtenthaler, S. F. (Corresponding author)DZNE*
Dataset: Beneficial effect of ACI-24 vaccination on microglial phenotypes in an amyloidosis mouse model
PRoteomics IDEntifications Database (2023)2023   Fulltext BibTeX | EndNote: XML, Text | RIS

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